THE INTERACTION WITH TUBULIN OF A SERIES OF STILBENES BASED ON COMBRETASTATIN A-4

A series of stilbenes, based on combretastatin A-4, were synthesised. A structure-activity study was carried out to characterise the interac tion of these agents with tubulin. The substitution of small alkyl sub stituents for the 4'-methoxy group of combretastatin A-4 and the loss of the 3'-hydroxyl group does not have a major effect on the interacti on with tubulin. trans-Stilbenes were shown to bind tubulin, but do no t inhibit microtubule assembly. This work, together with previous stud ies, has been used to propose an idealised structure for a tubulin-bin ding agent of this type.